Method for coating medical devices

ABSTRACT

An apparatus for coating medical devices at the point of care with a polymer and/or therapeutic agent comprising an environmentally controlled device coating chamber in which the device may be delivered by the manufacturer as the device packaging, or the device may be placed into the chamber at the point of care. The environmentally controlled chamber can provide a sterile enclosure in which the polymer and/or a therapeutic agent can be applied to an uncoated or previously coated device and converted to another form (such as a liquid to a film or gel) if desired, under controlled and reproducible conditions. The environmentally controlled chamber can accommodate and provide for coating the device by immersion, spray and other methods of covering the device surface with a liquid or powder. The chamber can provide for energy sources, both internally, such as heat produced by film heaters, and externally, such as UV light or microwave passing through the enclosure. The chamber may allow for changes in atmosphere to affect the coating, such as the introduction of certain gases and introducing pressure or vacuum.

This application is a continuation of U.S. patent application Ser. No.11/449,090 filed Jun. 8, 2006 now U.S. Pat. No. 7,781,010 which is adivisional of U.S. patent application Ser. No. 11/021,656 filed Dec. 23,2004, now U.S. Pat. No. 7,585,369, which claims the benefit of U.S.Provisional Patent Application No. 60/598,656 filed Aug. 4, 2004.

FIELD OF THE INVENTION

The present invention relates to the delivery of therapeutic agents froma coating, placed onto an implantable medical device at the point ofcare. More specifically, the present invention is directed to anenvironmentally controlled device coating and preparation chamber thatfacilitates the coating of a medical device with a drug and/or polymercoating at the point of care, prior to implantation into the body of ahuman or animal.

BACKGROUND OF THE INVENTION

Coating the surface of implanted medical devices with polymers and/ortherapeutic agents has become a common practice. In 2004, drug eludingcoronary stents are expected to comprise more than half of the over fourbillion dollar worldwide stent market. Therapeutic agents can enhancethe intended effect of the medical device, reduce or eliminate infectionor inflammation related to the device, accelerate or improve acceptanceof the device by the body, and/or treat specific diseases at the site ofthe device.

Medical devices which are implanted into the human body and whosefunction can be enhanced by therapeutic coatings include artificialjoints, fixation devices such as bone implants, artificial heart valves,pacemaker leads, dental implants and stents including cardiovascular,esophageal, and biliary.

Polymers and coatings such as phosphorycholine, hydrogels andhydroxyapatite, with and without additional therapeutic agents, arecommonly placed onto the surface of medical devices at the point ofmanufacture. While this practice delivers the device ready to use at thepoint of care, the coating and/or therapeutic agents are subjected tothe device sterilization process and the rigors of handling, shippingand storage. Many therapeutic agents, such as proteins, cannot survivethe device sterilization. Also, many therapeutic agents have relativelyshort shelf lives compared to the device itself, and when placed on thedevice at the point of manufacture, limit the shelf life and storagecondition of the device.

Larson et al., in U.S. Pat. No. 6,309,380, address the device point ofmanufacture therapeutic coating limitation problem by providing forapplication of the therapeutic coating at the point of care where andwhen the device is placed into the patient's body. This is accomplishedby coating the device at the point of care immediately prior toimplantation with a polymer and/or therapeutic agent and converting thecoating to a film by a chemical process or energy source such as heat orUV light. Larson et al. do not provide for applying a coating and/ordrug to the device at the point of care in a manner that reproduciblycontrols the device sterility and factors affecting variability of thecoating, and subsequently the drug delivery after implantation of thedevice.

SUMMARY OF THE INVENTION

The present invention is directed to an apparatus for coating medicaldevices at the point of care, such as in hospitals and medical clinics,for example, with a polymer and/or therapeutic agent. The inventionprovides for a point of care environmentally controlled device coatingchamber (ECDCC) in which the device may be delivered by the manufactureras the device packaging, or the device may be placed into the chamber atthe point of care. The environmentally controlled chamber provides asterile enclosure in which the solution containing polymer and/or atherapeutic agent can be applied to the device, and converted to a filmif desired, under controlled and reproducible conditions. Theenvironmentally controlled chamber of the invention can accommodate andprovide for coating the device by immersion, spray and other methods ofcovering the device surface with a liquid or powder. The chamber of thisinvention can provide for energy sources, both internally, such as heatproduced by film heaters, and externally, such as light (e.g. UV) ormicrowave passing through the enclosure. The chamber may allow forchanges in atmosphere to affect the coating, such as the introduction ofcertain gases and introducing pressure or vacuum. In addition, thepresent invention provides for an electronically, and/or manually,controlled machine (hereafter called a “docking station”) which can beused to electro-mechanically, and/or manually, hold, position, and/ormanipulate an ECDCC for the purpose of mixing medical device coatingmaterials, introducing one or more substances into an ECDCC, and/orotherwise controlling the environment for, and/or the process of, theapplication of therapeutic, and/or other substances to one or moremedical devices within an ECDCC.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the operator's panel and display of a dockingstation.

FIG. 2 shows the docking station side door and chamber process area withdoor in closed position.

FIG. 3 shows a view of the drive means end of the docking stationchamber process area.

FIG. 4 shows a view of the tailstock end of the docking station chamberprocess area.

FIG. 5 illustrates a cylindrical-shaped device coating chamber viewedfrom a coating process end.

FIG. 6 illustrates a cylindrical-shaped device coating chamber viewedfrom a mixing process end.

FIG. 7 represents a view into the interior of the coating process end ofa cylindrical-shaped device coating chamber.

FIG. 8 illustrates a mixing basket portion of a cylindrical-shapeddevice coating chamber.

FIG. 9 illustrates a mixing drive shaft and stopper from the mixingbasket of FIG. 8.

FIG. 10 shows a medical device attached to an interior surface of thecoating process end of a cylindrical-shaped device coating chamber.

FIG. 11 illustrates a cylindrical-shaped device coating chamberpositioned in a docking station for mixing of a coating.

FIG. 12 illustrates a cylindrical-shaped device coating chamberpositioned in a docking station for coating a medical device.

FIG. 13 is a view of a side and drive attachment end of an immersioncoating chamber.

FIG. 14 shows introduction ports of an immersion coating chamber.

FIG. 15 illustrates the magnetic drive mixer and mixing reservoir of animmersion coating chamber.

FIG. 16 illustrates the interior of the main body portion and immersionreservoir of an immersion coating chamber.

FIG. 17 shows a medical device support cover for attachment to animmersion reservoir of an immersion coating chamber.

FIG. 18 illustrates an immersion coating chamber positioned in a dockingstation for mixing of a coating.

FIG. 19 illustrates an immersion coating chamber positioned in a dockingstation for coating a medical device.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Coating a medical device with a therapeutic agent at the point of carerequires a process and procedure which delivers a reproducibly andcontrolled dose of the therapeutic agent and a coating which hasreproducible adhesion and mechanical properties. The coating processmust be done in a manner which preserves the sterility of the device,coating polymer and/or therapeutic agent. The application of energy tofacilitate the formation of coatings must be done in a manner that isuniform, reproducible and does not degrade the therapeutic agent. Inaddition, the placement of therapeutic agents onto the device at thepoint of care cannot be technique dependent nor require specializedskill or unusual attention by attending medical personnel. It isanticipated that many point of care device coatings, intended to providea therapeutic effect and enhance the action of the device, will beapplied to the device during or immediately prior to a surgery or otherinvasive procedures.

As stated above, the present invention is directed to an apparatus forcoating medical devices, such as with a polymer and/or therapeuticagent, at the point of care. The invention provides for a coatingchamber which is positionable in a docking station. The environmentallycontrolled device coating chamber may contain a port for adding thecoating material (while maintaining sterility of the device, chamber andsolution) and a heater to provide temperature controlled heat for thefilm formation process. It may also contain a stirring means (e.g. amagnetic field driven stirrer) for thoroughly mixing the polymer and thetherapeutic agent prior to the coating process. A second heater may becontained in the base of the coating chamber for heating the coatingsolution to a specific temperature before the coating process begins.The coating chamber can incorporate a reservoir, with or without aone-way valve, to trap excess polymer and/or therapeutic liquid orpowder during and after the coating process. The coating chamber can befabricated from materials such as certain plastics, which provide forthe passage of UV light and/or microwave energy to facilitate filmformation.

The coating chamber can be received by a docking station that canprovide timed and controlled energy (light, microwave, etc.) orelectrical power to the device, and a timed rotating magnetic field todrive the magnetic stirrer incorporated in the coating chamber and timedand controlled rotation of the coating chamber to facilitate completeand uniform distribution of the solution or powder on the device.

FIGS. 1-4 illustrate one aspect of the present invention comprising adocking station 2 into which various coating chambers (described below)are positionable for coating of a medical device. The docking station 2(FIG. 1) includes an operator's panel comprising an on-off switch 4, barcode reader 6, chip reader 8, swipe card reader 10 and indicator lights12. A mechanism to read information stored on a computer disc may alsobe included. A groove 14 is provided in the docking station chassis 15for a rollup door (shown with door “open”) and an electronicallycontrolled rollup door latch 16, 17 (FIG. 3) restricts and/or controlscoating processes so that the door remains closed during processing. Atouch screen interactive display 18 receives feedback, such as from aninternal level detector, and provides for an interactive readout such asfrom an out-of-level system lock.

As best seen in FIG. 2, the docking station 2 preferably includes apiano-style side door hinge 20, side door 22 and door latch 24,preferably electronically controlled. Further included is a rollup door26 (closed position) enclosing a coating chamber process area 28 (FIGS.3 and 4 with door 26 open) having one or more, preferably three,reflective interior surfaces 30 and one or more bulbs or other devices32 for introducing light, heat and/or microwave radiation to the chamber28.

FIGS. 3 and 4 also show the chamber process area 28 having ahorizontally mounted magnetic coating mixer drive unit 34, a verticallymounted magnetic coating mixer drive unit 36 (one or both drive units34, 36 may be present) and a computer controlled docking station drivehead 38 for rotating various styles of medical device coating chambersfor coating processes. Drive head 38 includes a drive socket 40, forengaging a cylindrical-style chamber mixing drive knob to spin themixer, and a plurality of introduction ports 42 (six shown) which matchthose in a coating chamber and allow the docking station toautomatically introduce pressure, special gases, and/or other elementsinto the chamber before, during, and/or after a coating is applied to amedical device. Docking station chassis 15 houses drive motors,electronics, etc. Drive head 38 and drive socket 40 may both be drivenby a single motor or may each be driven by a separate motor. A coatingchamber supporting tailstock 44 is also included as shown in FIG. 4.

FIG. 5 illustrates a cylindrical-shaped device coating chamber 50(viewed from a coating process end portion 55) which is positionable ina docking station 2 (FIGS. 3 and 4). The coating chamber 50 comprises achamber cylinder 51 having at one end thereof a support cover 52 with anarea of outside diameter 53 of the support cover 52 having abayonet-style attachment mechanism (not shown), or otherpositive-attachment means, which is configured to mate with the drivehead 38 of the docking station. Also located at one end of the chambercylinder 51 are a plurality of introduction ports 54 (six shown) incoating floor 59 for controlling the atmosphere, introducing gasesand/or other elements into the coating chamber before, during, and/orafter a coating is applied to a medical device.

The coating chamber 50 further includes a rotary door 56 which opens andcloses the introduction ports, either automatically or manually, such aswith a manual rotary door latch roll 58 which lifts up to be moved froman “open” to a “closed” position and back. Preferably, a manual rotarydoor latch roll spring 60 is mounted in a rotary door control tab 62 forholding the manual rotary door latch roll 58 against docking stationsupport cover 52 and in the “open position” and “closed position”grooves 64, 66 respectively, when the manual rotary door latch roll 58is not pulled up/away by pulling on control tab 62 which moves betweengrooves 64, 66 via slot 61. In FIG. 5, the manual version is shown withthe rotary door 56 in the “open” position. Of course, rotary door 56 maybe opened and closed by any suitable automatic means. Alternatively,each control port 54 may individually be opened and closed either mymanual or automatic means. FIG. 5 also shows the chamber 50 having afiltering pressure limiting vent port cover 68 having internal threadsto attach to any filtering pressure limiting vent port, attached viaboss 70 to the coating chamber 50, on any style of medical devicecoating chamber.

The other end of chamber cylinder 51 (mixing process end portion 57)includes a chamber mixer attachment cover 72 which holds a chamber mixerassembly in the mixing end of the chamber cylinder. Attachment cover 72has internal threads (or other positive-attachment means) which attachit to the chamber cylinder 51 and preferably includes an externalbayonet-style attachment mechanism (not shown), or otherpositive-attachment means, on outside diameter 74 of chamber mixingattachment cover 72 which allows attachment to the drive head 38 of thedocking station 2 during a mixing process. Cover 72 may include a largeaccess hole (not shown) to allow manual (or automated) loading andemptying of a chamber mixing basket (FIG. 8).

Both ends of the chamber cylinder 51 have a raised shoulder 76 withexternal threads (or other positive-attachment means) which engage withinternal threads (or other positive-attachment means) of docking stationsupport cover 52 on the coater end of the chamber 50, and with internalthreads (or other positive-attachment means) of the chamber mixerattachment cover 72 on the mixer end 57 of the chamber 50.

FIG. 6 illustrates the cylindrical-shaped device coating chamber 50viewed from its mixing process end portion 57 which includes a floor 78of the mixing basket, mixer drive shaft 80 and drive knob 82 whichengages drive socket 40 of the docking station 2 (FIG. 3) when thecoating chamber 50 is positioned in the docking station 2 for mixing(FIG. 8, discussed below). Mixing process end 57 also preferablyincludes one or more, preferably two, syringe port covers 84, 86 havinginternal threads (or other positive attachment) to attach to any syringeport on any coating chamber. In FIG. 6, syringe port cover 84 comprisesa needle penetration membrane and syringe port cover 86 is without aneedle penetration membrane. Preferably all syringe ports have anelectrical contact such that when the cover is replaced with a screw-in(or other positive attachment) syringe, a foil heater and/or temperaturesensor in the syringe can receive electrical power and/or computercontrol.

FIG. 7 represents a view into the interior of the coating process endportion 55 of a chamber cylinder 51. A plurality (six are shown) ofcoating vanes 88 are spaced, preferably equidistantly, about theinterior surface of the coating process end of the chamber cylinder 51.The coating vanes 88 lift a portion of coating mixture from bottom ofthe chamber as it rotates in the docking station, and the coatingmixture bathes, drips or splashes onto a medical device, coating itevenly. A leveling mechanism on the docking station insures the deviceis coated evenly. A foil heater 90 with temperature sensor (such as theThermofoil Heater/Sensor manufactured by Minco Products of Minneapolis,Minn.) may also be included. An internal opening 71 communicating withthe filtering pressure limiting vent port is also shown.

The mixing process end portion 57 of coating chamber 50 is furtherillustrated in FIG. 8. A mixing basket is formed by floor 78, basketcylinder 92, shoulder portion 94 and delivery end 96. The mixing basketis held in place in the chamber cylinder 51 by attachment cover 72 (FIG.6). The inner surface of the basket cylinder 92 includes mixing vanesarranged thereon. Delivery end 96 is opened and closed by a stopper 98,preferably conical in shape, which is actuated by axial movement ofmixer drive shaft 80 (FIG. 9) that extends between the drive knob 82 andthe stopper 98. Preferably, a spring (not shown) is placed between thefloor 78 and the base 83 of the drive knob 82 whereby the force of thespring urges the drive knob 82 away from floor 78 (to the right in FIG.8) thereby also urging stopper 98 into sealing engagement with the endof delivery end 96. Preferably, the distal portion of delivery end 96 isshaped so as to be complimentary with the form of the stopper 98 (e.g.both are conical) such that an adequate seal is, formed upon contact.

As seen in FIG. 9, preferably the drive shaft 80 includes a means suchas a spring pin 85 that cooperates with the appropriate detent surfaceson the inner surface of floor 78 to control the position of stopper 98.For example, clockwise rotation of drive knob 82 may result in thespring pin 85 encountering a stop surface. Further clockwise rotation ofthe drive knob 82 thereby results in the rotation of the entire mixingbasket as would be the case during the mixing process when the driveknob 82 is engaged with the drive socket 40 of docking station 2.However, the clockwise movement of the spring pin 85 imparts no movementof the drive shaft in the axial direction (the direction on the driveshaft 80) and thus, the stopper 98 remains closed against the deliveryend 96 by the action of the spring against the shoulder 83.

On the other hand, counterclockwise rotation of the drive knob 82, suchas turning by hand, may result in the spring pin 85 encountering asurface that inwardly tapers (i.e. toward delivery end 96) to a stopsurface. Movement of the spring pin 85 along the tapered surface resultsin the drive shaft 80, and hence the stopper 98, moving to the left inFIG. 8 against the force of the spring, thereby causing the stopper 98to disengage its seal with delivery end 96 and allow the contents of themixing basket to flow out and into the coating end 55 of the coatingchamber 50.

FIG. 10 shows an interior view of support cover 52, having interiorsurface 100, which together with the chamber cylinder 51 forms thecoating process end 55 (FIG. 5). The interior surface of floor 59includes a boss 102 and device attachment means 104 which is of a formappropriate for the particular device that is to be coated. In FIG. 10,the device shown is a prosthetic hip 106.

FIG. 11 illustrates a coating chamber 50 positioned in a docking station2 for mixing to occur in the mixing process end 57 of the coatingchamber. The drive knob 82 would be turned in the appropriate directionso that the stopper 98 was closed against delivery end 96 and thedesired components would be introduced through one or both ports 84, 86(FIG. 8). The coating chamber 50 is then positioned in the dockingstation 2 by inserting the drive knob 82 into drive socket 40 andplacing the support cover 52 in tailstock 44. The drive socket 40 isthen rotated causing rotation of the coating chamber 50 (and, hence,rotation of the mixing basket) thereby mixing the components previouslyplaced in the mixing basket. The rotational speed and duration areadjustable and are based on the components and mixing requirements.

Once mixing is complete, the coating chamber 50 is removed from thedocking station 2 and preferably positioned vertically with the mixingend 57 “up”. Drive knob 82 is then rotated as appropriate to open thestopper 98 (as discussed above) thereby resulting in the coating mixtureflowing from the mixing basket into the coating process end 55 of thecoating chamber 50.

After allowing an appropriate amount of time for emptying of the mixingbasket, the drive knob 82 is turned in a reverse direction to close thestopper 98 and the coating chamber 50 is returned to the docking station2 and positioned such that the coating process end portion 55 is engagedwith the drive head 38 and mixing process end portion 57 is engaged withtailstock 44 as is shown in FIG. 12. Drive head 38 is rotated, at adesired speed and for a desired time, thereby rotating the coatingchamber 50 (and therefore, of course, the coating process end 55). Thecoating vanes 88 (FIG. 7) lift a portion of coating mixture from bottomof the chamber as it rotates in the docking station 2, and the coatingmixture bathes, drips or splashes onto a medical device (such as anartificial hip shown in FIG. 10), coating it evenly. At an appropriatetime before, during and/or after coating, introduction ports 54 may beutilized for controlling the atmosphere, introducing gases and/or otherelements into the coating chamber.

Additionally, heat (or other energy necessary for curing, for example)may be introduced at a desired time from within the coating process end55 such as by heater 90 (FIG. 7) or via a source from within the chamber28 of docking station 2 (FIG. 3). Polymerization can be initiated by thedocking station 2 by applying energy (light or microwave), filteredand/or heated air through a chamber port, or electricity to heatingfoils internal to the chamber. Coating chamber 50 may be fabricated fromplastic through which light and/or microwave energy readily passes.Coating chamber 50 may have a medical device installed therein as partof its manufacturing process (hence, medical device is “packaged” in thecoating chamber) or a medical device may be installed at the point ofcoating.

While FIGS. 6-12 illustrate a bath, splash or drip type of coatingchamber, FIGS. 13 and 14 disclose an immersion coating chamber 110(which may be fabricated from plastics through which light and/ormicrowave energy may readily pass) comprising a generally cylindricalshaped main body portion 112 having a first end 113 closed by a wall 114and a second end closed by a wall 116 which may be removable.Alternatively, first end 113 may be closed by a removable cover which,upon removal, exposes a floor with introduction ports (similar to floor59 and ports 54 in FIG. 5) to align with ports 42 of the docking station2 when the coating chamber 110 is positioned in the docking station 2.The area adjacent the first end preferably includes an attachmentmechanism 118 such as a bayonet-style attachment mechanism (or otherpositive-attachment means) for engagement with the drive head 38 of adocking station 2 (FIG. 3).

Wall 116 preferably includes one or more ports with covers (FIG. 14)such as syringe port cover with needle penetration membrane 120, syringeport cover without needle penetration membrane 121 and filtering,pressure-limiting vent port cover 122. All covers have internal threads(or other positive attachment) to attach to any respective port on anydevice coating chamber. All syringe ports have an electrical contactsuch that, when the cover is replaced with a screw-in (or other positiveattachment) syringe, a foil heater and temperature sensor in the syringecan receive electrical power and/or computer control.

Immersion coating chamber 110 further includes a magnetic drive mixingreservoir portion 124 which houses a magnetic drive mixer. The mixingreservoir 124 is closed by a cover 126 which preferably has internalthreads (or other positive-attachment means) and which seals against theface of mixer reservoir 124. Located preferably diametrically oppositeof mixing reservoir 124 is an immersion reservoir portion 128 whichhouses an internal, electrically powered foil heater with temperaturesensor. Immersion reservoir 128 is dosed by a medical device supportcover 130 which preferably has an electrical connection, internalthreads (or other positive-attachment means) and which seals against theface of immersion reservoir 128. Medical device support cover 130supports and positions a medical device (such as a prosthetic heartvalve or cardiovascular stent) on a medical device attachment means andpreferably includes an internally mounted, electrically powered hotwirecoating trimmer.

In FIG. 15, magnetic drive mixing drive cover 126 is removed to show theinterior 132 of the magnetic drive mixing reservoir 124 and the magneticdrive mixer 134. Interior 132 may include a foil heater. Also visiblethrough first end 113 (open, with alternative cover removed and showinglocation 117 of floor with introduction ports), and through the interior115 of main body portion 112, is a medical device 136 (prosthetic heartvalve shown) mounted to medical device support cover 130 via attachmentmeans 138. An electrically powered and controlled foil heater withtemperature sensor 140 is shown positioned in the immersion coatingreservoir 128.

In FIG. 16, the medical device support cover 130 is removed from theimmersion reservoir 128 to show the interior 142 of the immersionreservoir. As appropriate, the inside of the immersion coating reservoir128 can be configured (such as with a recess and shoulder 144) so as toaccommodate a particular medical device support structure and attachmentmeans.

FIG. 17 shows a medical device support cover 130 comprising an area ofinternal threads 146 (or other positive-attachment means) for attachmentto immersion reservoir 128. As stated above, support cover 130 includesmedical device attachment means 138 to which is attached medical device136 (prosthetic heart valve shown), an electrically powered andcontrolled hotwire coating trimmer 148 and a boss 150 for positioningthe medical device attachment means 138 and hotwire coating trimmer 148within the coating reservoir 128. An immersion chamber 110 may have amedical device installed therein as part of the manufacturing process ora medical device may be installed at the point of coating.

FIG. 18 shows the immersion coating chamber 110 positioned in a dockingstation 2 whereby attachment mechanism 118 is engaged with drive head38. The coating chamber 110 is oriented by the drive head 38 such thatmagnetic drive mixing drive cover 126, and hence, magnetic drive mixer134 are positioned adjacent magnetic coating mixer drive unit 34 (FIG.3) whereby upon activation of mixer drive unit 34, components such aspolymers and/or therapeutic agents previously supplied to the mixingreservoir 124 will be appropriately mixed in accordance withinstructions provided to the controller of the docking station 2.

Upon completion of the mixing, the drive head 38 is activated to rotatethe immersion chamber 110 by 180 degrees to the position shown in FIG.19 wherein the prepared coating residing in mixing reservoir 124 flowsinto the smaller immersion coating reservoir 128 to immerse the medicaldevice supported on cover 130 in the coating. After a predeterminedamount of time, the immersion chamber 110 is again rotated by drive head38 to a position (such as back to the position shown in FIG. 18) wherebythe coating can drain from the medical device and from the immersioncoating reservoir 128 back into the mixing reservoir 124 thereby leavinga film on the medical device whose thickness is controlled by thesurface tension, density and viscosity of the coating. Additionally,heat (or other energy necessary for curing, for example) may beintroduced at a desired time from within the immersion coating reservoir128 such as by foil heater 140 or via a source from within the chamber28 of docking station 2 (FIG. 3). After the coating process is complete,the support cover 130 can be removed, providing access to the coateddevice.

Cured polymer flash adhering to device support can be addressed by theelectrically powered and controlled hotwire coating trimmer 148. Afterthe polymer film has been formed and polymerized or cured, the dockingstation can energize the resistance wire to burn off the polymer film atthe support member contact points. Additionally, cured polymer adheringto the chamber and adhering the chamber lid to the body may be addressedby equipping the docking station with a wrench type mechanism (notshown) into which the chamber lid can be inserted to assist the medicalpersonnel in disconnecting the chamber body from the lid.

In its simplest form, an immersion coating chamber may have the shape ofa cone, pyramid or trapezoid. The important aspect being that the mixingreservoir is of a size to hold sufficient coating mixture such that uponinverting the immersion chamber, the coating mixture will flow into thecoating reservoir and immerse the device to be coated. Of course, itshould be understood that if mixing of coating constituents is notnecessary, the coating composition may be introduced directly into thecoating process portion of a coating chamber (e.g. coating process endportion 57 or immersion coating portion 128).

In operation, the individual operating the docking station 2 and theimmersion coating chamber 110 (including an implantable medical devicethat was attached to cover 130 by the manufacturer, or alternatively,attached to cover 130 at the point of care), following interactiveinstructions on the touch screen 18 of the docking station 2, wouldinstall the immersion chamber in the docking station 2 by attaching thechamber opening 113 to the docking station drive head 38 (FIG. 18) viaattachment mechanism 118. Next, the operator would initiate a “coatingingredient loading cycle”, and the docking station 2 would position theimmersion chamber 110 so that its magnetic coating mixer 134 (and mixingreservoir 124) is down and its medical device coating reservoir 128 isup. Next, the operator would utilize the syringe ports 120 and/or 121 todeposit a pre-determined set of coating ingredients into the coatingchamber. Following that, the docking station rollup door would need tobe closed to then initiate the “coating mix cycle” by the magneticmixer. When mixing is complete, the docking station may pause until theoperator has initiated the “medical device coating cycle”, during whichdocking station drive head 38 would rotate the coating chamber 180degrees to immersion-coat the implantable medical device (FIG. 19). Thecoating chamber 110 would then be rotated back to the original positionand, possibly, the hot-wire coating trimmer may be activated. After thecoating is cured, the docking station 2 may direct the rotation of theimmersion coating chamber about 45 degrees so that the support cover 130with the coated medical device attached could be removed from theimmersion coating chamber, and so that the coated medical device couldthen be removed from the cover and implanted.

Example 1 Artificial Knee or Hip (an Orthopedic Implant)

The device is coated at the point of manufacture with Hydroxyapatite(HAp), a naturally derived material that makes up bone mineral and thematrix of teeth. Hydroxyapatite is biocompatible and can be coated ontothe surface of a medical device with porous properties that support theabsorption of therapeutic agents and their subsequent delivery after thedevice is implanted. The porous Hydroxyapatite coated medical device issterilized and delivered to the point of care in the chamber. Analternative bonding/linking technology for this example is to coat thedevice at the point of manufacture with a linker technology which bondfunctional peptides to biological materials and to synthetic materials.Linker technology is available from, for example, Affinergy Inc.,Research Triangle Park, N.C. A therapeutic protein to initiate abiological function related to the bone is added through the injectionports, mixed thoroughly in the chamber if required, heated to reducetheir viscosity if required after which the chamber rotates and bathesthe device in therapeutic agent for sufficient time, controlled by thedocking station, such that the therapeutic agent is absorbed by theHydroxyapatite coating or linked to the functional peptide. The dockingstation can then stop rotation and bathing of the device, allow forsufficient time for the device to drain, blow off excess therapeuticagent and dry the surface if desired, having maintained a sterileatmosphere throughout the process. This process allows for the deliveryof a therapeutic protein that may not have survived sterilization andwould have limited shelf life had it been applied at the point ofmanufacture.

Example 2 Heart Valve

A prosthetic heart valve is delivered, sterile, in an immersion chamber.At the point of care, an in vivo biocompatible and biodegradablepolymer, such as one produced from star shaped polylactide containing anethoxylate core and functionalized with acrylate and methacrylatependant groups, is injected into the chamber at the point of care. Thispolymer system is selected because of the ability to activate it withlight and change from a soft structure to a strong mechanical structurethat can withstand the flow and pressure of blood in the heart. Atherapeutic agent, such as an antimicrobial peptide is added either inconjunction and mixed with the polymer or in a separate step. Thedocking station then controls a process for mixing the polymer andtherapeutic agent, inverts the chamber through rotation such that theunmasked heart valve suture ring is saturated with thepolymer/therapeutic agent solution. After allowing sufficient time forabsorption into the suture ring and/or the coating of the suture ringsurface, the docking station then inverts the chamber such that theheart valve now drains of excess coating. After sufficient time forcomplete drainage, the docking station turns on the light source for atimed cure of the polymer then energizes the hot wire at the implantabledevice attachment points to burn of excess flash coating. The device hasnow been coated with an in vivo biodegradable coating containing aprotein based therapeutic agent.

Example 3 Cardiovascular Stent

A cardiovascular stent is coated at the point of manufacture withHydroxyapatite or a linker technology such as that offered by Affinergy,Inc. of Research Triangle Park, N.C., for example, and delivered to thepoint of care sterile in the shipping/coating chamber. At the point ofcare, a therapeutic agent to inhibit restenosis such as the VEGFreceptor KDR/flk-1 is added through the injection port of the chamber.Therapeutic agents such as KDR/flk-1 have advantages over proliferationinhibiting drugs in that peptides and proteins such as KDR/flk-1 preventrestenosis by accelerating the re-establishment of the proliferationdown-regulating endothelial tissue. Sterilization and shelf lifelimitations make difficult the application of peptides, proteins andbiological therapeutic agents at the point of manufacture. The chambercontaining the therapeutic agent and the stent is inserted into thedocking station which, by reading bar codes and/or imbedded chips,confirms the correct stent, coating and therapeutic agent then invertsthe chamber through rotation such that the hydroxyapatite stent coatingor the functional peptide linker is saturated with the therapeuticagent. After allowing sufficient time for absorption into the stentcoating or attachment to the functional peptide linker, the dockingstation then inverts the chamber such that the stent now drains ofexcess coating.

Example 4 Heart Valve

A heart valve is coated with functional peptide linker such as thatdeveloped by Affinergy, Inc. of Research Triangle Park, N.C., at thepoint of manufacture. Affinergy's functional peptide linker utilizes twocustom peptides linked together, one of which can selectively bind tosynthetic materials such as the sewing ring material (Dacron) of theheart valve and the other to a biological material (biologic). Thecoated heart valve is sterilized and delivered to the point of care.

While pre-coating a medical device prior to application of a finalcoating of a polymer and/or therapeutic agent has been discussed abovewith respect to linking, binding and absorbing types of pre-coatings,adsorbing types of pre-coatings, such as ion attracting types ofcoatings, are also contemplated as pre-coating compositions.

At the point of care, a biological therapeutic agent which acceleratesor stimulates the natural healing process and the production ofendothelial cells may be added. Examples of biologics for acceleratingthe formation or collection of endothelial cells include an antibodyspecific to the antigen cells that are in the blood which captures thepatients circulating endothelial progenitor cells in order to acceleratethe natural healing process. This antibody is available from BioInventInternational AB of Lund, Sweden and has been developed forcardiovascular stents by Orbus Medical Technology of Fort Lauderdale,Fla. A second example of a Biologic which can be attached to the heartvalve at the point of care, using the previous described peptide linkertechnology is the VEGF receptor KDR/flk-1 which is rate-limiting for afast regeneration of the endothelium resulting in an acceleration of thenatural healing process.

In this example of a point of care applied biologic, the inventiondevice described for applying a coating and therapeutic agent at thepoint of care is not needed as the biologic can be attached to thepeptide linker at the point of care by means such as direct immersioninto a container for a short non critical period of time

The present invention also contemplates a chamber of any shape whichutilizes atomized liquid or spray droplets to coat a device. Theatomized particles can be produced by an ultrasound transducer in thebase of a chamber, or in the docking station and acoustically coupled tothe chamber or by ultrasound atomizing nozzles, such as thosemanufactured by Sono-Tek Corporation in Milton, N.Y., in the chamber orin the docking station. Atomization can be accomplished in a containedatmosphere, thereby eliminating the hazard of airborne polymer andtherapeutic agents. Spray droplets can be produced by pressurized gasdelivering polymer and/or therapeutic agents to spray nozzlesdistributed throughout the chamber. A filter and/or filter collectionchamber on the chamber collects the polymer and therapeutic agent, thuspreventing their release into the atmosphere.

Polymer and/or therapeutic agents can be applied as atomized or spraydroplets in specific metered amounts (such as with equipment supplied bySono-Tek) or in excess whereby the excess is allowed to drain off thedevice, in which case, the coating thickness and drug delivery arecontrolled by the solution viscosity, density, surface tension and thechamber internal temperature.

Polymer and/or therapeutic agents can be conveniently added to a chamberat the point of care utilizing pre-filled syringes. A syringe withmultiple barrels of the same or different diameters can be pre-filledwith the polymer and therapeutic agent to be added at the point of careto the chamber. If a chemical reaction is required to cure the polymer,a three-chamber syringe can be provided with two chambers dedicated tothe polymer system and the third to the therapeutic agent. If a chemicalreaction is not required to cure the polymer, a two chamber syringe canbe provided with one chamber dedicated to the polymer and one to thetherapeutic agent. The barrel(s) dedicated to the polymers can beequipped with a one-way check valve so that the user may draw up thetherapeutic agent into that dedicated chamber only. The syringe may havean in-line mixing feature at the tip, mixing the contents of all barrelsas the syringe plunger is depressed. The syringe may be equipped with anexternal heating foil and thermistor to preheat the contents that willbe activated and controlled when placed in the docking station.

The docking station of the present invention addresses quality controland regulatory concerns of coating an implantable medical device at thepoint of care by delivering a reproducible process that is independentof user training or skill. The docking station capabilities includingone or more of the following:

-   -   provides a controlled process for coating an implantable medical        device at the point of care, independent of skill level or        training of the attending medical personnel;    -   reads barcodes, confirms drug, devices and process;    -   has the means to provide a level plane for even distribution of        coating;    -   mixing: the docking station can include a mixer;    -   rotation: chamber rotation insures even coverage of the device;    -   temperature control within the chamber and of the syringe        containing the polymer and/or therapeutic agent;    -   atmosphere control—gas, pressure and/or vacuum if required;    -   times and controls specific processes;    -   indicates stage of process and when cycles are complete;    -   coats a device by immersion (rotates chamber 180 degrees), bath        with rotation (such as 350 degree reversing rotation) for        uniformity, and/or atomizing spray heads;    -   delivers and controls energy to cure the polymer/therapeutic        agent coating by light, microwave and/or heat.

In addition, the coating chamber has capabilities which include one ormore of the following:

-   -   provides a sterile, robust container for shipping and inventory;    -   provides an environmentally controlled chamber for coating a        sterile implantable medical device with a polymer and/or        therapeutic agent at the point of care;    -   provides a means of distributing the coating uniformly over the        surface of the device by immersion, bathing the device and/or        spray;    -   provides a means of curing a polymer under controlled atmosphere        (vacuum or pressure, gas) and energy (heat, light and/or        microwave).

While the invention has been described with reference to preferredembodiments it is to be understood that the invention is not limited tothe particulars thereof. The present invention is intended to includemodifications which would be apparent to those skilled in the art towhich the subject matter pertains without deviating from the spirit andscope of the appended claims.

1. In a process of manufacturing a medical implant device, said processcomprising: applying at least one of a linking, binding, absorbing andadsorbing pre-coating to the device for subsequent coating of atherapeutic agent to the medical implant device, placing the pre-coatedmedical implant device in a coating chamber for subsequent applicationof a therapeutic coating at a point of care, sterilizing the medicalimplant device prior to delivering to a point of care, delivering thesterilized pre-coated device to a point of care in said coating chamber,loading said coating chamber into a coating apparatus, and applying atherapeutic coating on the sterilized pre-coated medical implant deviceat the point of care.
 2. The method of claim 1 wherein the pre-coatingcomprises a functional peptide linker or hydroxyapatite.
 3. The methodof claim 1 wherein said applying at least one of a linking, binding,absorbing and adsorbing pre-coating to the device occurs at a point ofmanufacture of said device.